MicroRNAs direct rapid deadenylation of mRNA

Wu, Ligang; Fan, Junmei; Belasco, Joel G.

doi:10.1073/pnas.0510928103

Cited by 1,003 publications

(830 citation statements)

References 32 publications

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“…In fact, miRNA-binding can clearly destabilize target mRNA by a mechanism distinct from the Argonaute-catalysed sequence specific cleavage that characterize RNAi (Bagga et al, 2005;Farh et al, 2005;Lim et al, 2005;Giraldez et al, 2006). Detailed analyses of miRNA-directed mRNA decay revealed that miRNAs induce translation-independent deadenylation of the targeted mRNA, which is the hallmark of deadenylation-dependent decapping followed by 5 0 -to-3 0 decay (Giraldez et al, 2006;Wu et al, 2006). Remarkably, AU-rich elements (ARE) in the 3 0 UTRs of unstable mRNAs can also accelerate the shortening of the poly(A) tail triggering decapping and RNA destruction, and there are hints of connections between the miRNA and ARE pathways.…”

Section: Mechanism(s) Of Mirna-mediated Gene Regulationmentioning

confidence: 99%

Principles and effects of microRNA-mediated post-transcriptional gene regulation

2006

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MicroRNAs (miRNAs) are abundant regulatory RNAs involved in the regulation of many key biological processes. Recent advances in understanding the mechanism of RNA interference and miRNA-mediated mechanisms shed light on major principals of the formation of the regulatory complex and provide models to explain how these small regulatory RNA species interfere with gene expression and how they influence the translational status of the transcriptome.

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Section: Mechanism(s) Of Mirna-mediated Gene Regulationmentioning

confidence: 99%

Principles and effects of microRNA-mediated post-transcriptional gene regulation

2006

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“…Recent studies have shown that miRNAs can regulate expression of their target genes by decreasing mRNA stability, in addition to translational inhibition (Yekta et al, 2004;Bagga et al, 2005;Wu et al, 2006). The strategy to identify target genes of miR-512-5p is shown in Figure 4a.…”

Section: Epigenetic Activation Of Mir-512-5pmentioning

confidence: 99%

Chromatin remodeling at Alu repeats by epigenetic treatment activates silenced microRNA-512-5p with downregulation of Mcl-1 in human gastric cancer cells

et al. 2009

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Epigenetic therapy using DNA methylation inhibitors and histone deacetylase (HDAC) inhibitors has clinical promise for the treatment of human malignancies. To investigate roles of microRNAs (miRNAs) on epigenetic therapy of gastric cancer, the miRNA expression profile was analysed in human gastric cancer cells treated with 5-aza-2 0 -deoxycytidine (5-Aza-CdR) and 4-phenylbutyric acid (PBA). miRNA microarray analysis shows that most of miRNAs activated by 5-Aza-CdR and PBA in gastric cancer cells are located at Alu repeats on chromosome 19. Analyses of chromatin modification show that DNA demethylation and HDAC inhibition at Alu repeats activates silenced miR-512-5p by RNA polymerase II. In addition, activation of miR-512-5p by epigenetic treatment induces suppression of Mcl-1, resulting in apoptosis of gastric cancer cells. These results suggest that chromatin remodeling at Alu repeats plays critical roles in the regulation of miRNA expression and that epigenetic activation of silenced Alu-associated miRNAs could be a novel therapeutic approach for gastric cancer.

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“…In addition to the slicer activity, miRNA can accelerate the target mRNA deadenylation and decapping thus affecting the translation initiation and transcript stability [28]. Translation is also indirectly regulated by spatial separation of miRNA-targeted mRNA complex from translational machinery into the cytoplasmic P-bodies, also known as processing bodies [29].…”

Section: Effector Stagementioning

confidence: 99%

Recent developments in understanding the mechanism and functions of microRNAs

Muzaffar¹,

Bisht²

2017

J App Biol Biotech

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Based on their mechanism of action and biological function, several classes of small RNAs have come into the limelight in the last two decades. These small RNA molecules generally belong to three main categories: short interfering RNAs (siRNAs), microRNAs (miRNAs), and piwi-interacting RNAs (piRNAs). miRNAs and siRNAs are distinguished primarily because miRNAs are endogenous in nature and are expressed by an organism's own genome, whereas siRNAs are exogenous in origin and derived mainly from the viruses and transposons. The first miRNA, lin-4, was discovered in 1993 as an endogenous regulator of genes that control developmental timing in Caenorhabditis elegans. miRNAs are coded by both plant and animal genomes and their transcription is typically performed by RNA polymerase II. MicroRNAs repress the expression of many genes by accelerating messenger RNA degradation as well as translational inhibition, thereby reducing the level of protein. Due to their involvement in various diseases like cancer, miRNAs have been a focus of scientific research for their potential as a new generation of drugs. The recent findings in miRNA research have been summarized in this review to add new dimensions to miRNA mechanism and functions.

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MicroRNAs direct rapid deadenylation of mRNA

Cited by 1,003 publications

References 32 publications

Principles and effects of microRNA-mediated post-transcriptional gene regulation

Principles and effects of microRNA-mediated post-transcriptional gene regulation

Chromatin remodeling at Alu repeats by epigenetic treatment activates silenced microRNA-512-5p with downregulation of Mcl-1 in human gastric cancer cells

Recent developments in understanding the mechanism and functions of microRNAs

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